RESUMO
Aim: In this work, mastoparan analog peptides from wasp venom were tested against Candida albicans and safety assays were performed using cell culture and model zebrafish. Materials & methods: Minimal inhibitory concentration was determined and toxicity was performed using human skin keratinocyte and embryo zebrafish. Also, permeation of peptides through embryo chorion was performed. Results: The peptides demonstrated anti-C. albicans activity, with low cytotoxicity and nonteratogenicity in Danio rerio. The compounds had different permeation through chorion, suggesting that this occurs due to modifications in their amino acid sequence. Conclusion: The results showed that the studied peptides can be used as structural study models for novel potential antifungal agents.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos/farmacologia , Venenos de Vespas/farmacologia , Animais , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/toxicidade , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Peptídeos/toxicidade , Venenos de Vespas/administração & dosagem , Venenos de Vespas/efeitos adversos , Venenos de Vespas/toxicidade , Peixe-ZebraRESUMO
Stings from the wasp Parachartergus fraternus occur throughout Latin America, and edema followed by pain is the main symptom presented by victims. This often limited inflammatory event has not been characterized for this species. In this work, we identified the mechanisms and possible mediators involved in this response. P. fraternus venom (100, 200, and 400 µg/kg) was injected into the hind paws of mice, and edema was evaluated at intervals of 10 min for up to 60 min and at 120, 240, and 1440 min using a digital plethysmometer. The peak of edema was observed at 10 min with a dose of 200 µg/kg. A reduction in edema was observed with indomethacin (58.1%), celecoxib (44.5%), MK886 (30.8%), and dexamethasone (53.2%). Loratadine, cimetidine, and cyproheptadine treatment reduced the edema by 54.2%, 63.9%, and 84.4%, respectively, compared with the control. Captopril and L-NAME inhibited 42.5% and 69.8%, respectively, of the edema. These results showed that the edema induced in mice by P. fraternus venom occurs early and is mediated by arachidonic acid derivatives, vasoactive amines, and nitric oxide. Together, these mediators amplify the inflammatory process, with emphasis on histamine and serotonin in triggering the edematogenic response, being more effective the use of cyproheptadine in the therapeutic approach.
Assuntos
Edema/induzido quimicamente , Venenos de Vespas/efeitos adversos , Animais , Captopril/farmacologia , Ciproeptadina/uso terapêutico , Edema/tratamento farmacológico , Histamina/farmacologia , Inflamação/etiologia , Inflamação/prevenção & controle , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Serotonina/farmacologia , VespasRESUMO
Anxiety disorders are major health problems in terms of costs stemming from sick leave, disabilities, healthcare and premature mortality. Despite the availability of classic anxiolytics, some anxiety disorders are still resistant to treatment, with higher rates of adverse effects. In this respect, several toxins isolated from arthropod venoms are useful in identifying new compounds to treat neurological disorders, particularly pathological anxiety. Thus, the aims of this study were to identify and characterize an anxiolytic peptide isolated from the venom of the social wasp Polybia paulista. The peptide was identified as Polisteskinin R, with nominal molecular mass [M+H](+)=1301Da and primary structure consisting of Ala-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH. The anxiolytic effect was tested using the elevated plus maze test. Moreover, adverse effects on the spontaneous behavior and motor coordination of animals were assessed using the open field and rotarod tests. Polisteskinin R induced a dose-dependent anxiolytic effect. Animals treated with the peptide and diazepam spent significantly more time into the open arms when compared to the groups treated with the vehicle and pentylenetetrazole. No significant differences in spontaneous behavior or motor coordination were observed between the groups, showing that the peptide was well tolerated. The interaction by agonists in both known BK receptors induces a variability of physiological effects; Polisteskinin R can act on these receptors, inducing modulatory activity and thus, attenuating anxiety behaviors. The results of this study demonstrated that the compound Polisteskinin R exerted potent anxiolytic effects and its analogues are promising candidates for experimental pharmacology.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Bradicinina/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Venenos de Vespas/uso terapêutico , Animais , Ansiolíticos/efeitos adversos , Ansiolíticos/isolamento & purificação , Ansiedade/psicologia , Bradicinina/efeitos adversos , Bradicinina/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos/métodos , Masculino , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/isolamento & purificação , Ratos , Ratos Wistar , Venenos de Vespas/efeitos adversos , Venenos de Vespas/isolamento & purificaçãoRESUMO
Stings by bees and wasps, including Brazilian species, are a severe public health problem. The local reactions observed after the envenoming includes typical inflammatory response and pain. Several studies have been performed to identify the substances, including peptides that are responsible for such phenomena. The aim of the present study is to characterize the possible nociceptive (hyperalgesic) and edematogenic effects of some peptides isolated from the venoms of the honeybee (Apis mellifera) and the social wasps Polybia paulista and Protonectarina sylveirae, in addition to characterize some of the mechanisms involved in these phenomena. For this purpose, different doses of the peptides mellitin (Apis mellifera), Polybia-MP-I, N-2-Polybia-MP-I (Polybia paulista), Protonectarina-MP-NH2 and Protonectarina-MP-OH (Protonectarina sylveirae) were injected into the hind paw of mice. Hyperalgesia and edema were determined after peptide application, by using an electronic von Frey apparatus and a paquimeter. Carrageenin and saline were used as controls. Results showed that melittin, Polybia-MP-I, N-2-Polybia-MP-I, Protonectarina-MP-NH(2) and Protonectarina-MP-OH peptides produced a dose- and time-related hyperalgesic and edematogenic responses. Both phenomena are detected 2 h after melittin, Polybia-MP-I, N-2-Polybia-MP-I injection; their effects lasted until 8 h. In order to evaluate the role of prostanoids and the involvement of lipidic mediators in hyperalgesia induced by the peptides, indomethacin and zileuton were used. Results showed that zileuton blocked peptide-induced hyperalgesia and induced a decrease of the edematogenic response. On the other hand, indomethacin did not interfere with these phenomena. These results indicate that melittin, Polybia-MP-I, N-2-Polybia-MP-I, Protonectarina-MP-NH(2), and Protonectarina-MP-OH peptides could contribute to inflammation and pain induced by insect venoms.
Assuntos
Venenos de Abelha/efeitos adversos , Abelhas/química , Mordeduras e Picadas/induzido quimicamente , Edema/induzido quimicamente , Hiperalgesia/induzido quimicamente , Venenos de Vespas/efeitos adversos , Animais , Venenos de Abelha/imunologia , Venenos de Abelha/isolamento & purificação , Mordeduras e Picadas/imunologia , Edema/imunologia , Humanos , Hiperalgesia/imunologia , Masculino , Camundongos , Dor/induzido quimicamente , Dor/imunologia , Venenos de Vespas/imunologia , Venenos de Vespas/isolamento & purificação , Vespas/químicaRESUMO
Background: Immunotherapy can be used to treat allergic reactions to insect stings, specially bees and wasps. Aim: To report the experience with immunotherapy with aqueous extracts of hymenoptera venoms (bees and wasps). Material and methods: Ten patients aged 6 to 58 years were treated in an allergy center of a University Clinical Hospital. The medical indication for this treatment was, in all patients, anaphylactic reactions after hymenoptera stings. Immunotherapy was carried out using standardized vaccines (Aqueous extracts Venomvac LETI, Spain), applied in a traditional protocol, with subcutaneous injections. This protocol had two phases: a buildup phase (between weeks 1 and 13) and a monthly maintenance phase, from the 13th week. The monthly maintenance dose was 100 fig of hymenoptera specific venom extract. Results: Six patients had adverse reactions of different severity, during the treatment protocols and all had a good response to immediate therapeutic measures. After these events, they followed the protocol without problems. Two patients, treated with bee vaccines, suffered an accidental bee sting during the maintenance phase and they developed only local reactions. Conclusions: The lack of adverse reactions to bee stings in these two patients indicates the acquisition of clinical tolerance.
Assuntos
Adolescente , Adulto , Animais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Venenos de Abelha/uso terapêutico , Dessensibilização Imunológica/métodos , Himenópteros/imunologia , Hipersensibilidade Imediata/terapia , Mordeduras e Picadas de Insetos/terapia , Venenos de Vespas/uso terapêutico , Anafilaxia/terapia , Venenos de Abelha/efeitos adversos , Venenos de Abelha/imunologia , Hipersensibilidade Imediata/imunologia , Mordeduras e Picadas de Insetos/complicações , Mordeduras e Picadas de Insetos/imunologia , Venenos de Vespas/efeitos adversos , Venenos de Vespas/imunologiaRESUMO
BACKGROUND: The reported prevalence of allergic systemic reactions to hymenoptera venom occur in up to 3.3% and large local reactions occur in 17% in the general population. OBJECTIVE: To investigate the prevalence of hymenoptera sting allergy in a group of veterinary medicine students from Monterrey, Nuevo Leon, Mexico. PARTICIPANTS AND METHODS: A transverse and observational study was done with 64 students of veterinary medicine. We conducted a questionnaire about the students' history of insect allergy and atopy. Skin test with allergenic extracts of bee and ant were practiced to all subjects. We performed aeroallergen skin prick test to the subjets with suspected atopy. RESULTS: Students age ranged from 17 to 25 years (mean 20.2) and 37 were males. Twenty students (31.3%) had clinical history of atopy and positive skin tests to aeroallergens. On the other hand, 5 students (7.8%), including 2 atopic, had suffered large local reactions, but none of them had suffered systemic reactions. Bee and ant skin tests were positive in 15.6% and 31.3% of the students respectively. There was no difference in the prevalence of hymenoptera allergy between atopic and non atopic subjects (p < 0.05). Further, the frequency of atopy in subjects with positive skin tests for bee and ant was 50%. CONCLUSION: The prevalence of large local reactions and hymenoptera sensitization found in this group was similar to that found in other epidemiologic studies.
Assuntos
Venenos de Formiga/efeitos adversos , Venenos de Abelha/efeitos adversos , Hipersensibilidade Imediata/epidemiologia , Mordeduras e Picadas de Insetos/imunologia , Estudantes de Ciências da Saúde , Medicina Veterinária , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/etiologia , Masculino , México/epidemiologia , Prevalência , Recidiva , Hipersensibilidade Respiratória/epidemiologia , Testes Cutâneos , Estudantes de Ciências da Saúde/estatística & dados numéricos , Venenos de Vespas/efeitos adversosRESUMO
BACKGROUND: Immunotherapy can be used to treat allergic reactions to insect stings, specially bees and wasps. AIM: To report the experience with immunotherapy with aqueous extracts of hymenoptera venoms (bees and wasps). MATERIAL AND METHODS: Ten patients aged 6 to 58 years were treated in an allergy center of a University Clinical Hospital. The medical indication for this treatment was, in all patients, anaphylactic reactions after hymenoptera stings. Immunotherapy was carried out using standardized vaccines (Aqueous extracts Venomvac LETI, Spain), applied in a traditional protocol, with subcutaneous injections. This protocol had two phases: a buildup phase (between weeks 1 and 13) and a monthly maintenance phase, from the 13th week. The monthly maintenance dose was 100 fig of hymenoptera specific venom extract. RESULTS: Six patients had adverse reactions of different severity, during the treatment protocols and all had a good response to immediate therapeutic measures. After these events, they followed the protocol without problems. Two patients, treated with bee vaccines, suffered an accidental bee sting during the maintenance phase and they developed only local reactions. CONCLUSIONS: The lack of adverse reactions to bee stings in these two patients indicates the acquisition of clinical tolerance.